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Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice
- Source :
- Pharmaceutical Biology, Vol 61, Iss 1, Pp 1082-1093 (2023)
- Publication Year :
- 2023
- Publisher :
- Taylor & Francis Group, 2023.
-
Abstract
- AbstractContext Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application.Objective This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis.Materials and methods Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings.Results Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1β and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1β, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment.Discussion and conclusion Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1β, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.
Details
- Language :
- English
- ISSN :
- 13880209 and 17445116
- Volume :
- 61
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Pharmaceutical Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7959cf9810e34004b272385162b47c29
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/13880209.2023.2233565